The nuclear envelope (NE) has long been appreciated as a gatekeeper to the genome of eukaryotic cells, restricting genomic access only to those molecules capable of traversing the NE via nuclear pore complexes (NPCs). It is increasingly evident, however, that the NE performs active and essential roles in genomic organization beyond providing simple compartmentalization of DMA. NE-associated complexes are important for maintenance of chromatin structure, gene regulation, and DMA replication. Disruption of the NE structure can lead to disregulation of these processes. This proposal focuses on the role of NE membrane proteins in maintaining the structural integrity provided by the NE, with a particular focus on the role of the transmembrane (TM) and lumenal domains of NE membrane proteins. [unreadable] [unreadable] [unreadable]